chr9-21991924-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_058195.4(CDKN2A):c.193+2215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 983,220 control chromosomes in the GnomAD database, including 77,739 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.46 ( 17719 hom., cov: 32)
Exomes 𝑓: 0.38 ( 60020 hom. )
Consequence
CDKN2A
NM_058195.4 intron
NM_058195.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.85
Publications
25 publications found
Genes affected
CDKN2A (HGNC:1787): (cyclin dependent kinase inhibitor 2A) This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
CDKN2A Gene-Disease associations (from GenCC):
- melanoma, cutaneous malignant, susceptibility to, 2Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- melanoma-pancreatic cancer syndromeInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
- familial atypical multiple mole melanoma syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- melanoma and neural system tumor syndromeInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.193+2215G>A | intron_variant | Intron 1 of 2 | ENST00000579755.2 | NP_478102.2 | ||
LOC124902130 | XR_007061436.1 | n.700G>A | non_coding_transcript_exon_variant | Exon 2 of 2 | ||||
CDKN2A | NM_001363763.2 | c.-4+2897G>A | intron_variant | Intron 1 of 2 | NP_001350692.1 | |||
CDKN2A | XM_047422597.1 | c.-4+2623G>A | intron_variant | Intron 1 of 2 | XP_047278553.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.461 AC: 70033AN: 151832Hom.: 17680 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
70033
AN:
151832
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.377 AC: 313138AN: 831270Hom.: 60020 Cov.: 25 AF XY: 0.377 AC XY: 144835AN XY: 383956 show subpopulations
GnomAD4 exome
AF:
AC:
313138
AN:
831270
Hom.:
Cov.:
25
AF XY:
AC XY:
144835
AN XY:
383956
show subpopulations
African (AFR)
AF:
AC:
11017
AN:
15748
American (AMR)
AF:
AC:
511
AN:
982
Ashkenazi Jewish (ASJ)
AF:
AC:
2069
AN:
5138
East Asian (EAS)
AF:
AC:
1152
AN:
3620
South Asian (SAS)
AF:
AC:
5664
AN:
16438
European-Finnish (FIN)
AF:
AC:
94
AN:
276
Middle Eastern (MID)
AF:
AC:
669
AN:
1618
European-Non Finnish (NFE)
AF:
AC:
281413
AN:
760218
Other (OTH)
AF:
AC:
10549
AN:
27232
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
9065
18130
27196
36261
45326
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
12252
24504
36756
49008
61260
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.462 AC: 70141AN: 151950Hom.: 17719 Cov.: 32 AF XY: 0.459 AC XY: 34047AN XY: 74248 show subpopulations
GnomAD4 genome
AF:
AC:
70141
AN:
151950
Hom.:
Cov.:
32
AF XY:
AC XY:
34047
AN XY:
74248
show subpopulations
African (AFR)
AF:
AC:
28023
AN:
41442
American (AMR)
AF:
AC:
7719
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
1441
AN:
3468
East Asian (EAS)
AF:
AC:
1695
AN:
5162
South Asian (SAS)
AF:
AC:
1621
AN:
4806
European-Finnish (FIN)
AF:
AC:
3534
AN:
10558
Middle Eastern (MID)
AF:
AC:
140
AN:
294
European-Non Finnish (NFE)
AF:
AC:
24600
AN:
67928
Other (OTH)
AF:
AC:
992
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1820
3640
5460
7280
9100
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
610
1220
1830
2440
3050
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1269
AN:
3476
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.